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Abstract Background SARS-CoV-2 belongs to the coronaviridae family and infects human cells by directly interacting with the angiotensin-converting enzyme-2 (ACE-2) through the viral Spike Protein (SP). While vaccines are crucial, much attention has been directed towards managing the symptoms of acute respiratory distress syndrome. Our present study highlights the potential in counteracting lung inflammation triggered by SARS-CoV-2 SP of the intranasal administration of the engineered probiotic Lactobacillus paracasei F19 expressing the enzyme NAPE-PLD (pNAPE-LP) able to in situ release palmitoylethanolamide (PEA) under a super-low boost of palmitate. Methods C57BL/6J mice undergo prophylactic treatment with intranasal pNAPE-LP/palmitate for 7 days before a 7 days challenge with intranasal SARS-CoV-2 SP. Then the capability of pNAPE-LP of colonizing the lungs and actively release PEA in situ have been determined by immunofluorescence, western blot and HPLC-MS. Moreover, the innate immune system downregulation and the histological damage rescue exerted by pNAPE-LP have been tested by immunofluorescence, hematoxylin and eosin staining, western blot analysis and ELISA test for the release of the pro-inflammatory mediators. Results pNAPE-LP effectively colonizes mice lungs and releases the anti-inflammatory compound PEA. Moreover, pNAPE-LP exhibits a protective effect on alveolar morphology, innate immune cells infiltration and in the reduction of neutrophil count, effectively reducing lung injury induced by SARS-CoV-2 SP. This is achieved by mitigating TLR4-mediated NLRP3 activation and the downstream pro-inflammatory products such as ILs, TNFα, C-reactive protein and the myeloperoxidase activity. Interestingly we observed a global reduction ACE2 expression in the lungs. Conclusion pNAPE-LP actively protect from severe inflammatory-related symptoms in SP-challenged mice. Also, it can downregulate the expression of ACE-2 receptors at the lung site potentially preventing the spreading of the infection.

Abstract Tuberculosis (TB) is one of the deadliest infectious disorders in the world. To effectively TB manage, an essential step is to gain insight into the lineage of Mycobacterium tuberculosis (MTB) and the distribution of drug resistance. Although the Campania region is declared a cluster area for the infection, to contribute to the effort to understand TB evolution and transmission, still poorly known, we have generated a dataset of 159 genomes of MTB strains, from Campania region collected during 2018–2021, obtained from the analysis of whole genome sequence. The results show that the most frequent MTB lineage is the 4 according for 129 strains (81.11%). Regarding drug resistance, 139 strains (87.4%) were classified as multi susceptible, while the remaining 20 (12.58%) showed drug resistance. Among the drug-resistance strains, 8 were isoniazid-resistant MTB, 4 multidrug-resistant MTB, while only one was classified as pre-extensively drug-resistant MTB. This dataset expands the existing available knowledge on drug resistance and evolution of MTB, contributing to further TB-related genomics studies to improve the management of this disease.

The aim of this essay is to offer new insights into Elena Ferrante’s poetics and aesthetic re-appropriations. Specifically, it focuses on the topic of “women who cross borders.” Women trespass boundaries on multiple levels: on an extra-textual level, the writer herself transgresses thresholds of national belonging between her alleged hometown of Naples – a powerful symbolic locus/location that comes to signify a sort of Mediterranean matrix – and the English-speaking world where her work has been highly praised. In visual media, her characters have crossed from the confines of the page to the frame of the transnational television screen in the Rai/HBO series adaptation of My Brilliant Friend (2018, 2020). Ferrante’s fictional women are also translated in the photography of American artist Francesca Woodman, which  powerfully (if unwittingly) foreshadows her poetics of frantumaglia and smarginatura. In this essay, I examine the ways in which Ferrante’s work and its transmedia translations interrogate the margin and its ambivalence in order to renegotiate complex and painful constructions of specifically feminine identities. In the process, I propose a new conceptualization of smarginatura. Rather than a dissolution or disappearance  of margins, I argue that smarginatura proves to be a crossing of borders towards different forms of belonging at multiple intersections of gender, class, culture, origins and place.

Abstract A flexible, fully organic detector for proton beams is presented here. The detector operates in the indirect mode and is composed of a polysiloxane-based scintillating layer coupled to an organic phototransistor, that is assessed for flexibility and low-voltage operation (V = −1 V), with a limit of detection of 0.026 Gy min−1. We present a kinetic model able to precisely reproduce the dynamic response of the device under irradiation and to provide further insight into the physical processes controlling it. This detector is designed to target real-time and in-situ dose monitoring during proton therapy and demonstrates mechanical flexibility and low power operation, assessing its potential employment as a personal dosimeter with high comfort and low risk for the patient. The results show how such a proton detector represents a promising tool for real-time particle detection over a large area and irregular surfaces, suitable for many applications, from experimental scientific research to innovative theranostics.

Measurement(s) Radiomic Features Technology Type(s) Digital Phantoms and Radiomic Software Tools

Toxoplasmosis, caused by the protozoan Toxoplasma gondii, is one of the main food-, water- and soil-borne zoonotic disease worldwide. Over the past 20 years many papers were published on the transmission of T. gondii by marine animals, including mollusks, which can concentrate the oocysts and release them. Sporulated oocysts may remain viable and infective for 18 months in seawater. Therefore, raw or undercooked bivalve mollusks pose a risk to humans. This study aimed to apply and validate for the first time a very sensitive digital droplet polymerase chain reaction (ddPCR) protocol to detect and quantify T. gondii DNA in mussels. Four concentration levels: 8000 genomic copies (gc)/μL, 800 gc/μL, 80 gc/μL, 8 gc/μL of a T. gondii reference DNA were tested. DNA was extracted from 80 pools of mussels (Mytilus galloprovincialis). Forty pools were contaminated with T. gondii reference DNA and used as positive controls, while 40 pools were used as negative controls. DdPCR reaction was prepared using a protocol, previously developed by the authors, for detection of T. gondii in meat. Amplification was obtained up 8 gc/μL. All infected replicates resulted positive, as well as no droplets were detected in negative controls. The droplets produced in the reaction ranged from 8,828 to 14,075 (average 12,627 droplets). The sensitivity and specificity of ddPCR were 100% (95%CI = 94.3–99.9). In addition, 100 pools of mussels collected in the Gulf of Naples were used to validate the protocol. Of these 16% were positive (95% CI = 9.7–25.0) for T. gondii. Samples were also tested by real-time PCR and no positive samples were found. Data obtained from ddPCR showed good identification of negative and positive samples with higher specificity and efficiency than real-time PCR. This tool could be very useful for a rapid sensitive detection of low DNA concentrations of T. gondii in mussels, reducing the risk of toxoplasmosis in humans.

Measurement(s) Calibration Factor • coefficient of variation • Texture Descriptor Technology Type(s) Single Photon Emission Computed Tomography • Image Feature

Nitric oxide (NO) is a short-lived gas molecule which has been studied for its role as a signaling molecule in the vasculature and later, in a broader view, as a cellular messenger in many other biological processes such as immunity and inflammation, cell survival, apoptosis, and aging. Fractional exhaled nitric oxide (FeNO) is a convenient, easy-to-obtain, and non-invasive method for assessing active, mainly Th2-driven, airway inflammation, which is sensitive to treatment with standard anti-inflammatory therapy. Consequently, FeNO serves as a valued tool to aid the diagnosis and monitoring of several asthma phenotypes. More recently, FeNO has been evaluated in several other respiratory and/or immunological conditions, including allergic rhinitis, chronic rhinosinusitis with/without nasal polyps, atopic dermatitis, eosinophilic esophagitis, and food allergy. In this review, we aim to provide an extensive overview of the current state of knowledge about FeNO as a biomarker in type 2 inflammation, outlining past and recent data on the application of its measurement in patients affected by a broad variety of atopic/allergic disorders.

Abstract The majority of local recurrences, after conservative surgery of breast cancer, occurs in the same anatomical area where the tumour was originally located. For the treatment of ductal carcinoma in situ (DCIS), a new medical device, named BAT-90, (BetaGlue Technologies SpA) has been proposed. BAT-90 is based on the administration of 90Y β-emitting microspheres, embedded in a bio-compatible matrix. In this work, the Geant4 simulation toolkit is used to simulate BAT-90 as a homogenous cylindrical 90Y layer placed in the middle of a bulk material. The activity needed to deliver a 20 Gy isodose at a given distance z from the BAT-90 layer is calculated for different device thicknesses, tumour bed sizes and for water and adipose bulk materials. A radiobiological analysis has been performed using both the Poisson and logistic Tumour Control Probability (TCP) models. A range of radiobiological parameters (α and β), target sizes, and densities of tumour cells were considered. Increasing α values, TCP increases too, while, for a fixed α value, TCP decreases as a function of clonogenic cell density. The models predict very solid results in case of limited tumour burden while the activity/dose ratio could be further optimized in case of larger tumour beds.

Abstract Glioblastoma (GBM) is the most lethal brain tumor in adults. Radiation, together with temozolomide is the standard treatment, but nevertheless, relapse occurs in nearly all cases. Understanding the mechanisms underlying radiation resistance may help to find more effective therapies. After radiation treatment, ATP is released into the tumor microenvironment where it binds and activates purinergic P2 receptors, mainly of the P2X7 subtype. Two main P2X7 splice variants, P2X7A and P2X7B, are expressed in most cell types, where they associate with distinct biochemical and functional responses. GBM cells widely differ for the level of P2X7 isoform expression and accordingly for sensitivity to stimulation with extracellular ATP (eATP). Irradiation causes a dramatic shift in P2X7 isoform expression, with the P2X7A isoform being down- and the P2X7B isoform up-modulated, as well as extensive cell death and overexpression of stemness and senescence markers. Treatment with P2X7 blockers during the post-irradiation recovery potentiated irradiation-dependent cytotoxicity, suggesting that P2X7B activation by eATP generated a trophic/growth-promoting stimulus. Altogether, these data show that P2X7A and B receptor isoform levels are inversely modulated during the post-irradiation recovery phase in GBM cells.

Abstract Backgorund Parents after Neonatal Intensive Care Unit (NICU) hospitalization of preterm infant may develop psychopathological symptoms. The aim of the study was to determine how parental stress and psychophysical wellbeing affect posttraumatic symptoms (PTTS) in parents during the first year after NICU discharge. Moreover, this study aimed to explore any gender-specific difference in psychological distress among mothers and fathers. Methods Prospective study design from September 2018 to September 2019. 20 pairs of parents of preterm infants admitted to a tertiary-level NICU were enrolled. Primary outcome was evaluation of PTTS in parents of preterm infants at one year after NICU discharge through Impact of Event Scale- Revised. Secondary outcomes were: impact of parental stress, psychophysical wellbeing, anxiety and depression respectively through Parental Stressor Scale: NICU, Short Form Health Survey-36(SF-36), Self-rating Anxiety Scale and Self-rating Depression Scale. Results Mothers experienced higher rates of PTTS than fathers across the first year after NICU discharge (55% vs 20%). Maternal avoidance symptoms were associated with perception of their own infant look. Emotional aspects linked to maternal role predicted 36,8% of their hyperarousal symptoms. Maternal PTTS severity was predicted by their social functioning. Paternal mental health was associated both with maternal and paternal intrusive symptoms.. Maternal stress was associated with paternal avoidance symptoms. Paternal mental health predicted their hyperarousal symptoms (40%) and PTSD severity (52%). Conclusions Parents who experienced NICU hospitalization of their own infant are at heightened risk to develop psychopathological symptoms. According to our initial hypothesis, investigating parental psychophysical wellbeing, through SF-36, originally provides a valuable support to detect parents at higher risk to develop posttraumatic outcomes across the first year after NICU discharge. In addition, paternal depression deserves to be taken into account since hospitalization as it could impact paternal PTSD development. Finally, these findings provide an initial evidence of gender-related patterns in PTSD development and psychological distress among mothers and fathers across the first year of their infant.

Companion animals are increasingly being recognised as important contributors to the spread of antimicrobial-resistant bacteria. The present work aimed to measure the antimicrobial drug prescribing in dogs and cats in the Campania Region, Italy by analysing the Veterinary Electronic Prescriptions (VEPs) between 2019 and 2020. The medical records associated with antimicrobial drug prescriptions were collected according to the drug administration (systemic or topical) and the rationale for the treatment chosen. In the period under investigation, 166,879 drugs were prescribed of which 129,116 (73.4%) were antimicrobial. A total of 83,965 (65%) antibiotics were prescribed to dogs, 40,477 (31.4%) to cats, and 4674 (3.6%) to other companion animals. In dogs, 90.5% of VEPs prescribed for systemic treatment included an antimicrobial Critically Important or Highly Important or Important for human medicine (WHO, 2018). The most widely prescribed class was fluoroquinolones. The antimicrobials prescribed were mainly metronidazole–spiramycin (29.7%), amoxicillin–clavulanic (19.6%), enrofloxacin and cephalexin in dogs (16.5%) and enrofloxacin (22.6%) and amoxicillin–clavulanic acid (21.4%) in cats. Based on the results, the widespread use of broad-spectrum antimicrobials and the use of molecules for which limitations should be observed according to the EMA guidelines has emerged.

Molecular Radiation Therapy (MRT) is a valid therapeutic option for a wide range of malignancies, such as neuroendocrine tumors and liver cancers. In its practice, it is generally acknowledged that there is a need to evaluate the influence of different factors affecting the accuracy of dose estimates and to define the actions necessary to maintain treatment uncertainties at acceptable levels. The present study addresses the problem of uncertainty propagation in 90Y-PET quantification. We assessed the quantitative accuracy in reference conditions of three PET scanners (namely, Siemens Biograph mCT, Siemens Biograph mCT flow, and GE Discovery DST) available at three different Italian Nuclear Medicine centers. Specific aspects of uncertainty within the quantification chain have been addressed, including the uncertainty in the calibration procedure. A framework based on the Guide to the Expression of Uncertainty in Measurement (GUM) approach is proposed for modeling the uncertainty in the quantification processes, and ultimately, an estimation of the uncertainty achievable in clinical conditions is reported.

Abstract Despite follicular lymphoma (FL) is frequently characterized by a moderate increase of glucose metabolism, PET/CT examinations provides valuable information for staging and response assessment of the disease. The aim of the study was to assess and compare the diagnostic performance of PET/ldCT and PET/ceCT, respectively, in evaluating FL patients at the end of treatment. Fifty FL consecutive patients who underwent end-of-therapy PET/CT with both ldCT and ceCT were analyzed. Two blinded observers independently assessed PET/ldCT and PET/ceCT applying the Deauville score (DS) and Lugano classification criteria. PET imaging obtained after the end-of-treatment (EoT) was classified as showing PET and ce-CT matched response (concordant imaging group, CIG) or PET and ce-CT unmatched response (discordant imaging group, DIG). Relapse rate and Event-Free Survival (EFS) were compared between CIG and DIG patients. Overall, no differences in metabolic response classification were observed between PET/ldCT and PET/ceCT. In 13 (26%) patients PET/ceCT identified additional FDG-negative nodal lesions in mesenteric, retroperitoneal and iliac regions. However, in all cases, final DS remained unchanged and the additional results did not modify the following therapeutic decision. Among patients, who obtained complete metabolic response a comparable rate of relapse was registered in DIG 3/13 (23%) and CIG subgroups 5/20 (25%) [p = 0.899]. In all 3 DIG cohort patients who relapsed the recurrent disease involved also, but not exclusively, PET negative lymph nodes detected by ceCT. In overall population metabolic response defined by PET/ldCT predicted EFS [76% (group of patients with metabolic response) vs 35% (group of patients with residual disease), p = 0.0013] significantly better than ceCT-Based response assessment [75% (group of patients with complete response) vs 53% (group of patients with residual disease), p = 0.06]. Our study demonstrates a negligible diagnostic and predictive value of ceCT performed in addition to standard 18FDG PET/ldCT for EoT response evaluation in FLs. PET/ldCT should be performed as first-line imaging procedure, also in patients with prevalent abdominal and pelvic involvement, limiting the acquisition of ceCT in selected cases. This tailored approach would contribute to avoid useless radiation exposure and preserve renal function of patients.

Measurement(s) sex cord-gonadal stromal tumor Technology Type(s) magnetic resonance imaging Sample Characteristic - Organism Homo sapiens Machine-accessible metadata file describing the reported data: https://doi.org/10.6084/m9.figshare.14511624

This essay starts from the idea that the correlation between Asian American subjectivity and exemplarity is an instance of race relations in the American context. The model minority myth represents Asian Americans as an example of successful assimilation into American society and simultaneously signals their exclusion from mainstream norms and ideals. In this essay I explore issues of representation, representativity, and access to narratives of identity choice by reading Yellow Face, the 2007 play written by David Henry Hwang. I first consider Hwang’s parody of identity politics and his staging of the racialization of bodies in contemporary “postracial” American society. Next, I discuss how dynamics of envy (Ngai 2005) enable a series of disidentificatory and antiproprietory practices, which ultimately disavow the iteration of a preestablished model subjectivity. Finally, I focus on the “melancholic condition” (Eng e Han 2000) as a political strategy of building and preserving communities within and beyond racial, class, and national boundaries.

Abstract Background Mood and metabolic disorders are interrelated and may share common pathological processes. Autonomic neurons link the brain with the gastrointestinal tract and constitute a likely pathway for peripheral metabolic challenges to affect behaviors controlled by the brain. The activities of neurons along these pathways are regulated by glia, which exhibit phenotypic shifts in response to changes in their microenvironment. How glial changes might contribute to the behavioral effects of consuming a high-fat diet (HFD) is uncertain. Here, we tested the hypothesis that anxiogenic and depressive-like behaviors driven by consuming a HFD involve compromised duodenal barrier integrity and subsequent phenotypic changes to glia and neurons along the gut-brain axis. Methods C57Bl/6 male mice were exposed to a standard diet or HFD for 20 weeks. Bodyweight was monitored weekly and correlated with mucosa histological damage and duodenal expression of tight junction proteins ZO-1 and occludin at 0, 6, and 20 weeks. The expression of GFAP, TLR-4, BDNF, and DCX were investigated in duodenal myenteric plexus, nodose ganglia, and dentate gyrus of the hippocampus at the same time points. Dendritic spine number was measured in cultured neurons isolated from duodenal myenteric plexuses and hippocampi at weeks 0, 6, and 20. Depressive and anxiety behaviors were also assessed by tail suspension, forced swimming, and open field tests. Results HFD mice exhibited duodenal mucosa damage with marked infiltration of immune cells and decreased expression of ZO-1 and occludin that coincided with increasing body weight. Glial expression of GFAP and TLR4 increased in parallel in the duodenal myenteric plexuses, nodose ganglia, and hippocampus in a time-dependent manner. Glial changes were associated with a progressive decrease in BDNF, and DCX expression, fewer neuronal dendritic spines, and anxiogenic/depressive symptoms in HFD-treated mice. Fluorocitrate (FC), a glial metabolic poison, abolished these effects both in the enteric and central nervous systems and prevented behavioral alterations at week 20. Conclusions HFD impairs duodenal barrier integrity and produces behavioral changes consistent with depressive and anxiety phenotypes. HFD-driven changes in both peripheral and central nervous systems are glial-dependent, suggesting a potential glial role in the alteration of the gut-brain signaling that occurs during metabolic disorders and psychiatric co-morbidity.

Background: The aim of this study was to compare, in users of bimodal cochlear implants, the performance obtained using their own hearing aids (adjusted with the standard NAL-NL1 fitting formula) with the performance using the Phonak Naìda Link Ultra Power hearing aid adjusted with both NAL-NL1 and a new bimodal system (Adaptive Phonak Digital Bimodal (APDB)) developed by Advanced Bionics and Phonak Corporations. Methods: Eleven bimodal users (Naìda CI Q70 + contralateral hearing aid) were enrolled in our study. The users’ own hearing aids were replaced with the Phonak Naìda Link Ultra Power and fitted following the new formula. Speech intelligibility was assessed in quiet and noisy conditions, and comparisons were made with the results obtained with the users’ previous hearing aids and with the Naída Link hearing aids fitted with the NAL-NL1 generic prescription formula. Results: Using Phonak Naìda Link Ultra Power hearing aids with the Adaptive Phonak Digital Bimodal fitting formula, performance was significantly better than that with the users’ own rehabilitation systems, especially in challenging hearing situations for all analyzed subjects. Conclusions: Speech intelligibility tests in quiet settings did not reveal a significant difference in performance between the new fitting formula and NAL-NL1 fittings (using the Naída Link hearing aids), whereas the performance difference between the two fittings was very significant in noisy test conditions.

Abstract This paper focuses on the understanding of the Random Telegraph Signal (RTS) in Single-Photon Avalanche Diodes (SPAD). We studied the RTS of two different SPAD layouts, designed and implemented in a 150-nm CMOS process, after proton irradiation. The two structures are characterized by different junction types: the first structure is constituted by a P+/Nwell junction, while the second is formed by a Pwell/Niso junction. RTS occurrence has been measured in about one thousand SPAD pixels and the differences addressed in two layouts are motivated and discussed. Hypotheses on the RTS origin are drawn by analyzing the RTS time constants and the RTS occurrence evolution as a function of the annealing temperature.

Abstract Background Recent developments in abscopal effect strongly support the use of radiotherapy for the treatment of metastatic disease. However, deeper understanding of the molecular mechanisms underlying the abscopal effect are required to best benefit a larger proportion of patients with metastasis. Several groups including ours, reported the involvement of wild-type (wt) p53 in radiation-induced abscopal effects, however very little is known on the role of wtp53 dependent molecular mechanisms. Methods We investigated through in vivo and in vitro approaches how wtp53 orchestrates radiation-induced abscopal effects. Wtp53 bearing (A549) and p53-null (H1299) NSCLC lines were xenotransplanted in nude mice, and cultured in 2D monolayers and 3D tumor spheroids. Extracellular vesicles (EVs) were isolated from medium cell culture by ultracentrifugation protocol followed by Nanoparticle Tracking Analysis. Gene expression was evaluated by RT-Real Time, digital qRT-PCR, and dot blot technique. Protein levels were determined by immunohistochemistry, confocal anlysis, western blot techniques, and immunoassay. Results We demonstrated that single high-dose irradiation (20 Gy) induces significant tumor growth inhibition in contralateral non-irradiated (NIR) A549 xenograft tumors but not in NIR p53-null H1299 or p53-silenced A549 (A549sh/p53) xenografts. We further demonstrates that irradiation of A549 cells in vitro induces a senescence-associated secretory phenotype (SASP) producing extracellular vesicles (EVs) expressing CD63 and carrying DNA:RNA hybrids and LINE-1 retrotransposon. IR-A549 EVs also hamper the colony-forming capability of recipient NIR A549 cells, induce senescent phenotype, nuclear expression of DNA:RNA hybrids, and M1 macrophage polarization. Conclusions In our models, we demonstrate that high radiation dose in wtp53 tumors induce the onset of SASP and secretion of CD63+ EVs loaded with DNA:RNA hybrids and LINE-1 retrotransposons that convey senescence messages out of the irradiation field triggering abscopal effect in NIR tumors.

Abstract How to differentiate with MRI-based techniques testicular germ (TGCTs) and testicular non-germ cell tumors (TNGCTs) is still under debate and Radiomics may be the turning key. Our purpose is to investigate the performance of MRI-based Radiomics signatures for the preoperative prediction of testicular neoplasm histology. The aim is twofold: (i), differentiating TGCTs and TNGCTs status and (ii) differentiating seminomas (SGCTs) from non-seminomatous (NSGCTs). Forty-two patients with pathology-proven testicular neoplasms and referred for pre-treatment MRI, were retrospectively enrolled. Thirty-two out of 44 lesions were TGCTs. Twelve out of 44 were TNGCTs or other histologies. Two radiologists segmented the volume of interest on T2-weighted images. Approximately 500 imaging features were extracted. Least Absolute Shrinkage and Selection Operator (LASSO) was applied as method for variable selection. A linear model and a linear support vector machine (SVM) were trained with selected features to assess discrimination scores for the two endpoints. LASSO identified 3 features that were employed to build fivefold validated linear discriminant and linear SVM classifiers for the TGCT-TNGCT endpoint giving an overall accuracy of 89%. Four features were employed to build another SVM for the SGCT-SNGCT endpoint with an overall accuracy of 86%. The data obtained proved that T2-weighted-based Radiomics is a promising tool in the diagnostic workup of testicular neoplasms by discriminating germ cell from non-gem cell tumors, and seminomas from non-seminomas.

Background & Aims: Acid hypersensitivity is claimed to be a symptomatic trigger in functional dyspepsia (FD); however, the neuroimmune pathway(s) and the mediators involved in this process have not been investigated systematically. Palmitoylethanolamide (PEA) is an endogenous compound, able to modulate nociception and inflammation, but its role in FD has not been assessed. Methods: Duodenal biopsy specimens from FD and control subjects, and peroxisome proliferator-activated receptor-α (PPARα) null mice were cultured at a pH of 3.0 and 7.4. Mast cell (MC) number, the release of their mediators, and the expression of transient receptor potential vanilloid receptor (TRPV)1 and TRPV4, were evaluated. All measurements also were performed in the presence of a selective blocker of neuronal action potential (tetradotoxin). FD and control biopsy specimens in acidified medium also were incubated in the presence of different PEA concentrations, alone or combined with a selective PPARα or PPAR-γ antagonist. Results: An acid-induced increase in MC density and the release of their mediators were observed in both dyspeptic patients and controls; however, this response was amplified significantly in FD. This effect was mediated by submucosal nerve fibers and up-regulation of TRPV1 and TRPV4 receptors because pretreatment with tetradotoxin significantly reduced MC infiltration. The acid-induced endogenous release of PEA was impaired in FD and its exogenous administration counteracts MC activation and TRPV up-regulation. Conclusions: Duodenal acid exposure initiates a cascade of neuronal-mediated events culminating in MC activation and TRPV overexpression. These phenomena are consequences of an impaired release of endogenous PEA. PEA might be regarded as an attractive therapeutic strategy for the treatment of FD.

The recent debate on the politics of life has developed in different directions, from Waste theory (Bauman, 2004) to Necropolitics (Mbembe 2004, 2019) and Butler’s idea of precariousness (2004, 2009). Despite their relevant differences, such critical perspectives reflect on how power has appropriated a semantics of disposability, superfluousness, and death. This essay explores the intersections of the US prison system, the abjection of colored lives, and Hawaiian Indigenous cultural resurgence. My chosen text for this exploration is Ciara Lacy’s powerful documentary Out of State (2017). The film follows a group of Native Hawaiian inmates to a private, for-profit prison, dislocated thousands of miles away from their island home, deep in the desert of Arizona. In this unfamiliar, barren space, Native Hawaiian inmates find a community and rediscover their cultural identities by teaching one another native culture, language, and traditional dance. As two of the men complete their sentences, the film uses their particular journeys for a much more universal story on the difficulty of re-entering a society that casts subjects into a residual existence. Lacy’s documentary thus complicates the logic of a clear separation between the inside and outside of prison. Yet, the film turns the metaphor of being out into a space of self-awareness and recognition that can eventually spark change.

Background and objectives: The ALS diagnosis requires an integrative approach, combining the clinical examination and supporting tests. Nevertheless, in several cases, the diagnosis proves to be suboptimal, and for this reason, new diagnostic methods and novel biomarkers are catching on. The 18F-fluorodeoxyglucose (18F-FDG)-PET could be a helpful method, but it still requires additional research for sensitivity and specificity. We performed an 18F-FDG-PET single-subject analysis in a sample of familial ALS patients carrying different gene mutations, investigating the genotype-phenotype correlations and exploring metabolism correlations with clinical and neuropsychological data. Methods: We included ten ALS patients with pathogenic gene mutation who underwent a complete clinical and neuropsychological evaluation and an 18F-FDG-PET scan at baseline. Patients were recruited between 2018 and 2022 at the ALS Tertiary Centre in Novara, Italy. Patients were selected based on the presence of ALS gene mutation (C9orf72, SOD1, TBK1, and KIF5A). Following a validated voxel-based Statistical Parametric Mapping (SPM) procedure, we obtained hypometabolism maps at single-subject level. We extracted regional hypometabolism from the SPM maps, grouping significant hypometabolism regions into three meta-ROIs (motor, prefrontal association and limbic). Then, the corresponding 18F-FDG-PET regional hypometabolism was correlated with clinical and neuropsychological features. Results: Classifying the patients with C9orf72-ALS based on the rate of disease progression from symptoms onset to the time of scan, we observed two different patterns of brain hypometabolism: an extensive motor and prefrontal hypometabolism in patients classified as fast progressors, and a more limited brain hypometabolism in patients grouped as slow progressors. Patients with SOD1-ALS showed a hypometabolic pattern involving the motor cortex and prefrontal association regions, with a minor involvement of the limbic regions. The patient with TBK1-ALS showed an extended hypometabolism, in limbic systems, along with typical motor involvement, while the hypometabolism in the patient with KIF5A-ALS involved almost exclusively the motor regions, supporting the predominantly motor impairment linked to this gene mutation. Additionally, we observed strong correlations between the hypometabolism in the motor, prefrontal association and limbic meta-ROI and the specific neuropsychological performances. Conclusions: To our knowledge, this is the first study investigating brain hypometabolism at the single-subject level in genetic ALS patients carrying different mutations. Our results show high heterogeneity in the hypometabolism maps and some commonalities in groups sharing the same mutation. Specifically, in patients with C9orf72-ALS the brain hypometabolism was larger in patients classified as fast progressors than slow progressors. In addition, in the whole group, the brain metabolism showed specific correlations with clinical and neuropsychological impairment, confirming the ability of 18F-FDG-PET in revealing pattern of neuronal dysfunction, aiding the diagnostic workup in genetic ALS patients.

As of October 2022, the COVID-19 pandemic continues to pose a major public health conundrum, with increased rates of symptomatic infections in vaccinated individuals. An ideal vaccine candidate for the prevention of outbreaks should be rapidly scalable, easy to administer, and able to elicit a potent mucosal immunity. Towards this aim, we proposed an engineered Escherichia coli (E. coli) Nissle 1917 (EcN) strain with SARS-CoV-2 spike protein (SP)-coding plasmid, which was able to expose SP on its cellular surface by a hybridization with the adhesin involved in diffuse adherence 1 (AIDA1). In this study, we presented the effectiveness of a 16-week intragastrically administered, engineered EcN in producing specific systemic and mucosal immunoglobulins against SARS-CoV-2 SP in mice. We observed a time-dependent increase in anti-SARS-CoV-2 SP IgG antibodies in the sera at week 4, with a titre that more than doubled by week 12 and a stable circulating titre by week 16 (+309% and +325% vs. control; both p < 0.001). A parallel rise in mucosal IgA antibody titre in stools, measured via intestinal and bronchoalveolar lavage fluids of the treated mice, reached a plateau by week 12 and until the end of the immunization protocol (+300, +47, and +150%, at week 16; all p < 0.001 vs. controls). If confirmed in animal models of infection, our data indicated that the engineered EcN may be a potential candidate as an oral vaccine against COVID-19. It is safe, inexpensive, and, most importantly, able to stimulate the production of both systemic and mucosal anti-SARS-CoV-2 spike-protein antibodies.